High density lipoprotein (HDL) can be separated into distinct particles based on apolipoprotein content. The present study compares the in vivo metabolism of the 125I or 131I-labeled apoE-containing HDL particles LpE, LpE:A-I, LpE:A-II and LpE:A-I:A-II in controls and subjects with abetalipoproteinemia lacking apoB, by: study 1) injection of apoE particles purified from normolipidemic plasma; study 2) injection of apoE particles lacking apoB into normolipidemic subjects; and study 3) injection of apoE particles purified from abetalipoproteinemic plasma into abetalipoproteinemic subjects. The fractional catabolic rates in study 1 were for LpE:A-I, LpE:A-II and LpE:A-I:A-II, 2.67+/-0.37 d-1, 2.28+/-0.39 d-1 and 1.73+/-0.33d-1, respectively (p<0.005 for LpE:A-I vs. LpE:A-I:A-II); in study 2 for LpE, LpE:A-I, LpE:A-II and LpE:A-I:A-II, 3.33+/-0.37d-1, 3.08+/-0.35-d, 2.58+/-0.60d-1 and 2.47+/-0.44d-1, respectively (p<0.001 for LpE vs. LpE:A-I:A-II, p<0.05 for LpE vs. LpE:A-II, p<0.02 for LpE:A-I vs. LpE:A-I:A-II); and in study 3, for LpE and LpE:A-I:A-II, 3.58+/-0.48d-1 and 2.77+/-0.29d-1, respectively. ApoE-containing HDL particles were catabolized rapidly, and at a similar rate in normolipidemic and abetalipoproteinemic subjects, suggesting that the rapid catabolism is not explained by VLDL-IDL-LDL metabolism. Thus, the results of this study show that apoE-containing HDL particles are catabolized much more rapidly than apoA-I-containing HDL, with LpE<LpE:A-I<LpE:A-II<<LpE:A-I:A-II<< LpA-I<LpA-I:A-II. The presence of apoE changes the metabolic pathways of the particles, possibly by exposing them to the action of lipolytic enzymes, and promoting their uptake by hepatic receptors recognizing apoE.